Ignite Creation Date:
2024-05-05 @ 11:37 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00094302
Status:
COMPLETED
Last Update Posted:
2015-03-02
First Post:
2004-10-15
Brief Title:
Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function
Sponsor:
Carelon Research
Organization:
Carelon Research
Study Overview
Official Title:
Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist TOPCAT
Status:
COMPLETED
Status Verified Date:
2014-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
TOPCAT
Brief Summary:
The purpose of this study is to evaluate the effectiveness of aldosterone antagonist therapy in reducing cardiovascular mortality aborted cardiac arrest and heart failure hospitalization in patients who have heart failure with preserved systolic function
Detailed Description:
BACKGROUND
Heart failure HF is a major cause of morbidity and mortality particularly in older people Indeed it is the most common discharge diagnosis in patients older than 65 years As the United States population ages heart failure will continue to grow as a public health concern Therapeutic trials of heart failure have dealt almost exclusively with patients who have systolic dysfunction However there is now an emerging awareness that nearly half of the patients with heart failure have preserved systolic function and that the survival of these patients is adversely affected This study is a randomized clinical trial of a novel therapeutic approach specifically the use of spironolactone an aldosterone antagonist in treating these patients While this treatment has been shown to be useful in treating heart failure with reduced systolic function it has not been studied in patients with preserved systolic function
Patients with heart failure and preserved systolic function have a poor prognosis The annual mortality rate is intermediate between the prognosis for those without heart failure and for those with heart failure and reduced systolic function For instance Family Health Study participants with heart failure and preserved systolic function had a mortality rate of 9 compared to 3 for their age- and gender-matched controls The mortality rate was 19 in heart failure patients with reduced systolic function heart failure compared to 4 for their matched controls
As heart failure develops neurohormones are released that initially improve cardiac output but ultimately contribute to progression of left ventricular dysfunction The renin-angiotensin-aldosterone system is an important part of this compensatory response Aldosterone levels may rise to 20 times normal levels in heart failure and aldosterone contributes to the development of myocardial fibrosis Spironolactone is a potassium-sparing diuretic that acts on the distal tubule inhibiting sodium and potassium ion exchange There are several potential beneficial actions including prevention of cardiac fibrosis A recent trial evaluated spironolactone in patients with systolic dysfunction heart failure Spironolactone treatment caused a 30 reduction in mortality compared to placebo p 0001 The improvement resulted from a reduction in all cause mortality More recently the Eplerenone Post-Myocardial Infarction MI study showed that this aldosterone antagonist significantly reduces mortality despite background treatment with an angiotensin-converting enzyme ACE inhibitor and beta-blocker Advantages of using spironolactone in this study are that it is commercially available inexpensive and no longer under patent therefore this study will not be done by industry Also there is a clear physiologic rationale for its use and the side effect profile is well understood The study enrolled subjects who had preserved systolic function with heart failure and who met clearly defined eligibility criteria that were selected to make the results widely generalizable to clinical practice
DESIGN NARRATIVE
This is a randomized double-blinded placebo-controlled trial of aldosterone antagonist therapy 15 mg dose spironolactone or placebo titrated up to 30 or 45 mgday in 3445 adult patients with heart failure and preserved systolic function Patients were recruited from August 2006 through January 2012 treated and will be followed through June 2013 Approximately 270 clinical sites in six countries were subcontracted by the clinical trial coordinating center Subject visits to a clinical center will occur every four or six months Data collected include demographic and clinical data including the results of history and physical exams laboratory and imaging data repository specimens for special physiology studies and genetic studies Additionally data regarding quality of life and compliance with assigned treatment will also be collected and assessed
Heart failure HF is a major cause of morbidity and mortality particularly in older people Indeed it is the most common discharge diagnosis in patients older than 65 years As the United States population ages heart failure will continue to grow as a public health concern Therapeutic trials of heart failure have dealt almost exclusively with patients who have systolic dysfunction However there is now an emerging awareness that nearly half of the patients with heart failure have preserved systolic function and that the survival of these patients is adversely affected This study is a randomized clinical trial of a novel therapeutic approach specifically the use of spironolactone an aldosterone antagonist in treating these patients While this treatment has been shown to be useful in treating heart failure with reduced systolic function it has not been studied in patients with preserved systolic function
Patients with heart failure and preserved systolic function have a poor prognosis The annual mortality rate is intermediate between the prognosis for those without heart failure and for those with heart failure and reduced systolic function For instance Family Health Study participants with heart failure and preserved systolic function had a mortality rate of 9 compared to 3 for their age- and gender-matched controls The mortality rate was 19 in heart failure patients with reduced systolic function heart failure compared to 4 for their matched controls
As heart failure develops neurohormones are released that initially improve cardiac output but ultimately contribute to progression of left ventricular dysfunction The renin-angiotensin-aldosterone system is an important part of this compensatory response Aldosterone levels may rise to 20 times normal levels in heart failure and aldosterone contributes to the development of myocardial fibrosis Spironolactone is a potassium-sparing diuretic that acts on the distal tubule inhibiting sodium and potassium ion exchange There are several potential beneficial actions including prevention of cardiac fibrosis A recent trial evaluated spironolactone in patients with systolic dysfunction heart failure Spironolactone treatment caused a 30 reduction in mortality compared to placebo p 0001 The improvement resulted from a reduction in all cause mortality More recently the Eplerenone Post-Myocardial Infarction MI study showed that this aldosterone antagonist significantly reduces mortality despite background treatment with an angiotensin-converting enzyme ACE inhibitor and beta-blocker Advantages of using spironolactone in this study are that it is commercially available inexpensive and no longer under patent therefore this study will not be done by industry Also there is a clear physiologic rationale for its use and the side effect profile is well understood The study enrolled subjects who had preserved systolic function with heart failure and who met clearly defined eligibility criteria that were selected to make the results widely generalizable to clinical practice
DESIGN NARRATIVE
This is a randomized double-blinded placebo-controlled trial of aldosterone antagonist therapy 15 mg dose spironolactone or placebo titrated up to 30 or 45 mgday in 3445 adult patients with heart failure and preserved systolic function Patients were recruited from August 2006 through January 2012 treated and will be followed through June 2013 Approximately 270 clinical sites in six countries were subcontracted by the clinical trial coordinating center Subject visits to a clinical center will occur every four or six months Data collected include demographic and clinical data including the results of history and physical exams laboratory and imaging data repository specimens for special physiology studies and genetic studies Additionally data regarding quality of life and compliance with assigned treatment will also be collected and assessed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| HHSN268200425207C | OTHER_GRANT | NIH contract | None |